Multiple sclerosis (MS), an inflammatory demyelinating disease of the central system (CNS), is the most common cause of primary non- traumatic neurological disability among young adults in North America and Europe. Tissue injury in MS is contingent upon inflammation, mediated by invading hematogenous T cells and monocytes. Chemokines are small secreted peptides that exert chemoattractant effects by interacting with specific high-affinity receptors on leukocytes. Chemokine expression is central to leukocytes trafficking: specific chemokines and chemokine receptor systems determine the composition of inflammatory infiltrates. Relatively little is known about chemokine expression in multiple sclerosis (MS) however. Prior work documented chemokine induction in experimental autoimmune encephalomyelitis (EAE) and recent work from our lab demonstrated specific patterns of chemokine and chemokine receptor expression within the CNS of MS patients during periods of active inflammation. Our data implicate specific chemokines and receptors in CNS inflammatory processes in MS and suggest key hypothesis, to be examined by specific aims that address: 1) Chemokine receptors on T cells and mononuclear phagocytes in MS brain; 2) Chemokine receptors on MNCs in blood and brain of marmosets with EAE; 3) The relationship between chemokines, their receptors and disease activity in MS patients. The proposed studies will clarify the role of specific chemokine and chemokine receptor systems in inflammatory processes in MS. We will concentrate primarily on determining chemokine receptor expression by T cells and macrophages. The rationale for this focus is that receptor blockade is the most practical near-term approach to therapeutic intervention to preclude chemokine action in human inflammatory disease.